Short Communication

British Journal of Cancer (2008) 99, 6–13. doi:10.1038/sj.bjc.6604436 www.bjcancer.com
Published online 24 June 2008

Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses

A Sultana1, C Tudur Smith1,2, D Cunningham3, N Starling3, J P Neoptolemos1 and P Ghaneh1

  1. 1CRUK Liverpool Cancer Trials Unit, Cancer Research Centre, 200 London Road, Liverpool, L3 9TA, UK
  2. 2Centre for Medical Statistics and Health Evaluation, University of Liverpool, Shelley's Cottage, Brownlow Street, Liverpool L69 3GS, UK
  3. 3Department of Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK

Correspondence: Dr P Ghaneh, Division of Surgery and Oncology, School of Cancer Studies, 5th Floor-UCD Building, Daulby Street, Liverpool, Merseyside L69 3GA, UK. E-mail: p.ghaneh@liv.ac.uk

Revised 28 April 2008; Accepted 2 May 2008; Published online 24 June 2008.

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Abstract

In advanced pancreatic cancer, level one evidence has established a significant survival advantage with chemotherapy, compared to best supportive care. The treatment-associated toxicity needs to be evaluated. This study examines the secondary outcome measures for chemotherapy in advanced pancreatic cancer using meta-analyses. A systematic review was undertaken employing Cochrane methodology, with search of databases, conference proceedings and trial registers. The secondary end points were progression-free survival (PFS)/time to progression (TTP) (summarised using the hazard ratio (HR)), response rate and toxicity (summarised using relative risk). There was no significant advantage of 5FU combinations vs 5FU alone for TTP (HR=1.02; 95% CI=0.85–1.23) and toxicity. Progression-free survival (HR 0.78; CI 0.70–0.88), TTP (HR=0.85; 95% CI=0.72–0.99) and overall response rate (RR=0.56; 95% CI=0.46–0.68) were significantly better for gemcitabine combination chemotherapy, but offset by the greater grade 3/4 toxicity thrombocytopenia (RR=1.94; 95% CI=1.32–2.84), leucopenia (RR=1.46; 95% CI=1.15–1.86), neutropenia (RR=1.48; 95% CI=1.07–2.05), nausea (RR=1.77; 95% CI=1.37–2.29), vomiting (RR=1.64; 95% CI=1.24–2.16) and diarrhoea (RR=2.73; 95% CI=1.87–3.98). There is no significant advantage on secondary end point analyses for administering 5FU in combination over 5FU alone. There is improved PFS/TTP and response rate, with gemcitabine-based combinations, although this comes with greater toxicity.

Keywords:

meta-analyses, pancreatic cancer, chemotherapy